We plan four groups of studies dealing with both basic and clinical aspects of iron nutrition during growth and development: 1. Experiments dealing with the systemic manifestations of iron deficiency will focus on determining why a brief period of iron deficiency in the young rat can lead to a long-lasting and probably permanent deficiency of non-heme iron in the brain. First we will try to define the critical period in the maturation of the brain when the deficiency in non-heme iron can occur, what parts of the brain are affected and the conditions that make the defect irreversible. Next, we will investigate the basis for these changes using chemical and isotopic methods in the study of cell and membrane pemeability to iron and the turnover non-heme protein in brain. 2. The possibly harmful effects of iron excess on the ability of neutrophils to kill bacteria will be investigated as a function of the iron saturation of transferrin in the suspending medium and lactoferrin in the neutrophil granules. The experimental design will involve modifications of the media in a standard test of bacterial killing by neutrophils. 3. Clinical studies will involve a detailed analysis of iron nutrition in infancy, making use of the assay for serum ferritin, a new and potentially important means of evaluating iron nutrition within and near the physiological range, in conjunction with other measures of iron nutrition. The goal of these studies is to determine the medicinal iron requirements (if any) of breast-fed babies and the need for iron-fortification in formula-fed infants during the first year of life. These requirements must be redefined in the light of the recent improvement in bioavailability of iron added to infant cereals. 4. Experiments in the rat are planned to characterize in detail the newly established role of serum ferritin in iron transport. An understanding of the kinetic role of serum ferritin should allow a more sophisticated use of the assay in the study of iron nutrition and of diseases which affect iron metabolism. We believe that the type of information that we plan to accumulate will help to provide a sound basis for the development of new recommendations for iron nutrition during infancy and childhood.